The last decade of developments in the field of clinical analyzers has seen a trend away from wet assays using liquid reagents, to dried ones using slide test elements. The purpose, of course, is to eliminate liquids and their attendant difficulties in handling. This need to avoid liquids has become even more important, as non-Earth environments became sites for such analyzers. For example, bulk liquids create a serious handling problem in the zero gravity environment of space.
The slide test elements available under the trademark "Ektachem" test elements, assayed on analyzers available under the trademark "Ektachem" analyzers, both from Eastman Kodak Company, have largely eliminated the noted liquid handling problems. There remains, however, even with such test elements the need to deposit a small quantity of patient sample liquid onto the test element. That quantity in turn must somehow be obtained from a larger patient sample reservoir. Aspirating probes with disposable tips have been used for this purpose. Because such tips have to be wetted on the outside to aspirate sample into the inside, this pre-wetting of the tips has led to the need for removal of exterior liquid that can otherwise cause perfusion. (Perfusion is the deflection of liquid dispensed from a probe tip, up the outside surface of the tip instead of onto a receiving slide test element).
A variety of techniques have been used to control the liquid on the exterior surface to prevent perfusion. One of the most common has been to configure the structure of the tip to discourage exterior liquid from remaining in position to affect the dispensing operation. Examples are described in U.S. Pat. No. 4,347,875. Such tips can be further provided with a wax coating to discharge retention of exterior liquid, also as described in said '875 patent, column 5. Yet another technique is to "cut", i.e., blow, the exterior liquid away with an air knife, as described in U.S. Pat. No. 4,615,360. Still another technique is to absorptively wipe off the tip each time liquid is aspirated or dispensed, but wiping creates serious problems in automated apparatus and biohazards.
With the exception of the wiping technique, each of the aforementioned solutions has met with considerable success. Nevertheless, another source of perfusion remains. That is, the aspirating probe is intended to dispense the small quantity of patient sample as a steady stream, onto an object or surface such as a dried test element. The stream must not proceed too fast, lest it puddle on the surface and encourage perfusion by wetting the tip exterior. It must not proceed too slowly, lest the stream break apart into droplets that can spatter upon impact, and provide unexpected distribution on the test element that forms ringing. Unfortunately, the rate of acceptance of the stream into the test element, which of course is the controlling factor governing this problem, depends on some variables: the wettability of the surface of the slide test element, the fluid characteristics of the patient sample, and the tip-to-element spacing.
Of these variables, the variation in wettability of the test element is a predictable function of the chemistry of that element. That in turn is dictated by the assay to be run, a factor that the analyzer can keep track of. Presumably, if this were the only controlling variable, the analyzer could be reset with a certain tip-to-element spacing, each time a new chemistry is presented to the probe. This, however, presumes that close manufacturing tolerances have been used, so that the desired reset spacing will in fact be achieved each time. Because such close tolerances are a major cost burden, resetting the spacing to a fixed value is not considered an adequate solution. In addition, even if cost were not a factor, such fixed resetting will not accommodate the problem created by patient sample variations. That is, the liquid surface tension of the samples is normally not known in advance and hence is not a datum that is entered with the patient I.D. Great variations in surface tension occur in, e.g., blood serum, primarily due to the existence of the very diseased states that are sought to be detected.
Yet another problem with conventional analyzers has been that the slide test element on which the sample liquid is to be dispensed, can be bowed out of its nominally planar configuration. This in turn will adversely affect the tip-to-element spacing that needs to be controlled to provide optimum stream flow. Such bowing is also difficult to detect or predict in advance.
Therefore, there has been a great need prior to this invention to provide a dispensing station for an analyzer that can automatically adjust the tip-to-element spacing regardless of which of the above-noted factors has changed in an unpredictable way.
Pressure transducers have been used with dispensing probes in prior analyzers. For example, in U.S. Pat. No. 4,340,390, a pressure transducer is described to sense, among others, things such as plugged probes, and the complete separation of the fluid or liquid that is in the probe, from the test element, column 7, lines 18-20. This sensing technique, in which the pressure registers as "zero" due to the complete break, is also used in the '390 invention to indicate completion of the dispensing step.
Still other uses have been made of such transducers, as described, for example, in U.S. Pat. No. 4,675,301. That is, inadvertent pressure changes within the probe are monitored so that the liquid meniscus always starts from about the same position for the dispensing step. Such a procedure however does not address the problems of spacing between probe and test element discussed above. Instead, it assumes that pre-set spacings will be satisfactory. As described above, this is not always the case.
Finally, a recent use of pressure transducers is described in U.S. Pat. No. 4,794,085. Such a system causes the dispenser to pressurize (or draw a vacuum on) the air in the tip at a certain height to sense if the empty tip has yet contacted liquid to be aspirated. Once contact is achieved, the pressure reading will change. Such a system is not satisfactory to handle the intercept of a full tip's liquid, with either a liquid or a solid, since a full tip cannot readily alter the interior pressure to sense the exterior conditions.
Thus, the conventional use of pressure transducers has not solved the need for automatic adjustment of tip-to-element spacing described above.